UA79741C2 - Method for removing impurities from 2-nitro-4-methylsulfonylbenzoic acid, purified 2-nitro-4-methylsulphonylbenzoic acid and process for preparation of mesotrione - Google Patents

Abstract

A method for removing impurities from 2-nitro-4-methylsulfonylbenzoic acid which comprises at least two of the following steps, in any order, (a) dissolving 2-nitro-4-methylsulfonylbenzoic acid in water at pH of about 3 to 10, followed by filtration; (b) contacting an aqueous solution of 2-nitro-4- methylsulfonylbenzoic acid with activated carbon at pH of about 2 to 10; (c) treating an aqueous solution of 2-nitro-4-methylsulfonylbenzoic acid with sufficient base to hydrolyze undesired nitro and dinitro substituted impurities.

Description

The present invention relates to a method of obtaining - (5) contacting an aqueous solution of 2-nitro-4-methylsulfonylbenzoic acid with activated methylsulfonylbenzoic acid of a high degree of purity, to purified 2-nitro-4-carbon at a pH of approximately 2 -10; of methylsulfonylbenzoic acid, which is obtained - (c) treatment of an aqueous solution of 2-nitro-4- in this way, to the method of obtaining mesotri-methylsulfonylbenzoic acid with a sufficient amount of it using a purification method, after which the amount of base for the hydrolysis of unwanted nitro- and using the following stages, and to meso-dinitro substituted impurities; sawdust obtained in this way. - with further aging of the obtained water

Mesotrione (2-(4-methylsulfonyl-2-one solution containing 2-nitro-4-nitrobenzoyl)cyclohexane-1,3-dione) is methylsulfonylbenzoic acid, a triketone compound useful as a herbicide up to approx. 95"7С and adjusting the pH is indicated for grain crops, which is used for the solution to a pH sufficient for pre-emergence and post-emergence control of herbaceous weeds and crystallization of 2-nitro-4-methylsulfonylbenzoic rock-leaved weeds: acid during cooling. Preferably, before cooling and crystallization, the pH is adjusted to approx.

MO i o lisno 1.

The same; With the help of this invention, it is possible to remove impurities that are typically found in 2-nitro-4-methylsulfonylbenzoic acid, or those that have been found to contribute to a positive

Mesotrione can be obtained first of the mutual result in the Ames test in the final product with the medium of 2-nitro-4-methylsulfonylbenzoic acid of zotrione. - (MMeVA); To maintain the temperature of the resulting solution containing 2-nitro-4-

Mo, Gi methylsulfonylbenzoic acid, the specified solution is usually heated; however, it is possible to carry out the reaction at a sufficient temperature in such a way that heating is not required. approximately 852C, resulting in the corresponding acid chloride at approximately 952C, i.e. In the method according to the present invention, preferably,

Figure Z Y | are stages (a) and (B) used when using

Chlorohydric acid, which is an intermediate between stages (a) and (c), when stages (p) are used, can then interact with /1,3- and (c) when stages (a), (B) are used and (c), or cyclohexanedione in the presence of a cyanide catalyst, especially when used in the order of the jam stage and triethylamine to obtain crude (a), (b) and (c). mesotrione. Solvents can be removed by distillation, and mesotrione is precipitated from the reaction mixture. and, optionally, drying the indicated crys- by centrifugation. talc 2-nitro-4-methylsulfonylbenzoic acid

It was found that mesotrione, obtained from talot. in any way, can show positive results. It is also preferable when at stage (a) the pH is measured in the Ames test. To my surprise, it was found to be up to about 3-7. that this is not a quality characteristic of mesotrione itself. At stage (a), the base is preferably chosen from as well as not the result of side products, from the group consisting of potassium hydroxide, hydrolyzed as a result of the reaction described above, and of calcium, ammonium hydroxide, sodium carbonate really occurs due to impurities in the source and sodium bicarbonate. MM5BA materials. To solve this problem and In addition, preferably, when at stage (B) of the acti- obtaining the product of mesotrione, which shows wove coal is in the form of powder or a negative result in the Ames test, it would be desirable- granules. It is also preferable, when at stage (p), an aqueous solution of 2-nitro-4-methylsulfonylbenzoic acid MMZVA, so that such impurities can be removed, is passed through a column that is filled with such impurities. tive coal.

Accordingly, the present invention offers a method of de- In the preferred embodiment of the invention, removal of impurities From 2-nitro-4- solid substance MM5BA is dissolved in water at a pH of at least two of the following stages, in any insoluble substance. The obtained solution is in what order: brought into contact with powdered activated carbon - (a) dissolution with 2-nitro-4-carbon at a pH of approximately 3-8 to remove methylsulfonylbenzoic acid in water at a pH of phenolic, nitro, and nitrophenolic impurities. After about 2-10 with further filtration; additional filtration, the resulting solution is further

carried out in alkaline conditions for the hydrolysis of impurities or suspensions with moderate stirring. In dogs, there are nitro- and dinitro-analogues of MM5BA, which can be present as a result of synthesis methods, which can be mixed with 56 g of caustic soda at a speed of 2 ml per minute to dissolve solid re- are used, which lead to MMZBA. The solution. The mixture is left to stir and is heated, preferably, to about 90-95, within 30 minutes until all solids dissolve, the pH is brought to about 1 with the help of organic substances with the formation of a milky-white mixture at the pH of organic/inorganic acids, such as orthophosphoric, 3 ,65. oxalic, formic, malic, saline, nitric, The obtained mixture was filtered through a filter - sulfuric acid, but preferably, with the help of rolling paper M/paytap 4 in a Buchner funnel in sulfuric acid, and allowed to cool to room conditions under a vacuum of 50 mm Hg. with obtaining transparent temperature. The resulting crystalline MMZVA can be obtained from a clear amber-colored mother solution. to filter, rinse and dry. The mother liquor was again filtered through a filter

In accordance with this invention, also offering paper U/paytap 25 in the Buchner funnel contains purified MM5BA, which is obtained, or which is under vacuum conditions. The mother liquor returned to can be obtained by the specified method. reactor and added 10 g of activated carbon

In accordance with the present invention, the offer- Saydop 2? 10x40. The mixture was stirred with a measured method of obtaining mesotrione, which includes a speed to prevent coal abrasion, removal of impurities with MM5BA by the method described for 2 hours at 30"C. The coal mixture was filtered above, and then the transformation of the obtained clean- at pH 4.0 through filters M/paytap 44 and 5, MMZBA was converted into mesotrione. One known method for removing spent coal is the interaction of MM5BA with 1,3-la and residual small coal particles. cyclohexadione in such a way as to obtain a Clear mother liquor was returned to the il mesotrione. The corresponding general methods are described, the reactor and 7.1 g of 2595 Maon were loaded there for example, in (EP 805792, EP 805791 and 05 62185791. raising the pH from 4.1 to 13, 0. An alkaline mixture that has

As a rule, there is no direct reaction - a darker color was left for a moderate interaction of MMZVA with dione at an acceptable speed, and stirring at 30"C for 1.5 hours with the aim of thus, MMZVA is first converted into hydrolysis of impurities - an excess of nitrated analogs, a more reactive derivative, such as halogenated MM5BA. hydride or acid anhydride. One such way is the mixture was acidified at a temperature surrounding the transformation of MM5BA into a suitable excess medium, loading 5.1 g of 4095 acid chloride using chloride Hg25Ox, with pH 13 to pH 3.6, and began to heat to a source, for example, thionyl chloride or, preferably, 907"C. When the temperature reached 90"C, the mixture of phosgene, and then the interaction of this anhydride was again acidified from pH 3.6 to pH 0.8. The resulting acid solution with 1,3-cyclohexanedione was slowly cooled to 60"C and then cooling mesotrione. The interaction of acid chloride with a shaft in an ice bath to ambient temperature with cyclohexanone can be carried out, for example, in the presence of a cyanide catalyst and triethylamine. The resulting suspension was filtered through a funnel, although other methods are also known. In such a Buchner apparatus, solvents are usually removed by distillation and UMpaytap 244 with the help of a filter paper. The filter element mesotrione is precipitated twice from the reaction mixture, which was washed with 3000 ml of tap water and dehydrated, using several stages of regeneration. From the mixture, approximately 112.5 g of pH solution was isolated and isolated by filtration or centrifugation of solids. Solids are then dried by grouting. According to the method given overnight in a vacuum oven at 60" with the invention, a method is also proposed, which allows obtaining 90 g of a powdery substance to avoid obtaining an Ames-positive meso-amber color. The output after purification was sawn by using the above-mentioned descent - 94,796. The obtained substance was converted into a medium for the purification of MM5BA, which is then used to obtain mesotrione, which shows a negative result in the test, as described above. According to the present invention, and Example 2, an Ames-negative mesotrione is proposed , Method combined in one reaction vessel - obtained or obtainable in this way This example illustrates a method of purifying 2-

The following examples are intended for il-nitro-4-methylsulfonylbenzoic acid of the invention and should not be considered as such, (MM5BA) combined in one reaction vessel. that limit it. In a glass round-bottomed reaction vessel with a capacity of

Example 1 tyu 2l, which is equipped with a paddle stirrer, on

This example illustrates the method of purification of 2- heating jacket, condenser, thermometnitro-4-methylsulfonylbenzoic acid, which rum, 902ml of water and 100g of crude is loaded in one reaction vessel. MM5BA to form a suspension. In the suspension for

61g of 2595 Mahon solution was loaded into a round-bottomed glass reaction vessel with a capacity of 1L, which is equipped with a paddle stirrer, and the pH is adjusted to 3.7. The mixture was filtered through a funnel with a mometer, a heating jacket, a condenser, a Buchner with filter paper U/paytap 44 and a pH electrode and a 100 ml dropping funnel, and a white precipitate was collected on the filter paper. Zboml of water was loaded with further loading. The filtrate was again filtered through a filter with 100 g of powdered MM5BA from the obtained paper M/paytap Zh5. Transparent mother solution ro-

were divided into two equal factions. 5 g of activated carbon was added to one fraction, and no 2-nitro-4-methylsulfonylbenzoic material was added to one fraction. acid using the procedure described

The fraction with coal was mixed for 2 in Example 1, while the treatment stages included hours at ambient temperature, dissolution, filtration of undissolved impurities, even at pH 3.7 and then filtered in a Buch funnel, hydrolysis, crystallization, separation and drying. nera through filter paper Mpaitap 44 and 5. 2- there is an allocation:

The mother liquor was returned to the reactor and loaded into a round-bottomed reaction vessel with a capacity of 5. 90 g of 2595 Mahon solution was added to the liter. to 90"C. 206g of solid 2-nitro-4-0.8 were added to the hot mixture using a 500-ml dropping funnel, 175ml of 4095 sulfuric acid was added to the pH and slowly cooled for crystallization of methylsulfonylbenzoic acid and 1800g of water mixed . The suspension was filtered and solids to form a suspension. Then it was washed through the dropper and dried. 125g of 2595 Mahon solution was added to the funnel for the pH of the second fraction (without coal), the dissolution of solids was increased at pH 3.5. The result was from 3.7 to 13 in 92 g of 2595 Mahon solution and heated, and the mixture was filtered twice through a Bühne funnel to 90"C for several minutes. 180g of 4095 sulfuric acid for Upaytap 25 2.5 micron was added to the hot mixture, which was equipped with filter paper, with the result that 2172g was obtained, reducing the pH from 13 to 0.8. A mixture of slowly cooled filtrate with a pH of 3.5. chewed to crystallize the product. The obtained solution of sodium salt of 2-nitro-4-vinyl MM5BA from the fractions was separated by filtration of methylsulfonylbenzoic acid and divided into two equal fractions of 1086 bg each on a Buchner funnel with filter paper. To faction (A)

UMpantap 244. The filter element was washed, 33 g of activated carbon was added, heated to 2x100 with tap water and dehydrated. At 90°C, slowly loading 210 ml of solution 4090, the alkaline element was dried in a vacuum oven at 607°C of sulfuric acid through a dropping funnel to pH for 4 hours. From the fraction with coal, 0.9 was obtained. At this pH value, the mixture formed 43.2 g of dry MM5BA, and from the fraction without coal - 44.3 m of suspension with large crystals.

This means the extraction yield of 92 and 9495, respectively. 10 g of activated carbon obtained during one hour from these fractions, purified MMZVA, was transformed at ambient temperature into a product of mesotrione and tested with moderate stirring and left overnight for activity in the Ames test. The products showed nega- sedimentation before removing the spent tive response in the Ames test. coal by filtering through a sinter funnel

Example From 40 micron glass. The filtrate was crystallized at

This example illustrates a method of purifying 2- ambient temperature, slowly nitro-4-methylsulfonylbenzoic acid with 195 ml of 4095 sulfuric acid solution, which is described in Example 2. through a dropping funnel at a pH of 0.89. At this-

Different loadings of the product were used, and the pH value of the mixture formed a suspension with de-

MM5BA, which are 20, 30 and 5095, with relatively smaller crystals than fraction (A). before initial loading when using suspensions obtained from fractions (A) and (B) separately with the following stoichiometry: filtered through a Buchner funnel, which provides

Loading ММЗВА with filter paper U/paytap 24. Volo-

The sample element from each filtration was washed twice

Materials: ZbOml of tap water, dehydrated and dried

Crude MM5BA (9095) was heated in a vacuum oven overnight at 40°C. Fractions

Tap water (A) and (B), respectively, gave 90 and 88 g of purified 2-2595 mainN, g(rn3i,5) nitro-4-methylsulfonylbenzoic acid. These 2595 maonN, g(рн13) fractions were converted into mesotrione, which showed 4095 Н25ОХ, g a negative result in the Ames test.

Activated carbon, g (Saidop 10x40) Example 5

The obtained batches yielded 28, 74 and 90 g of the product.

MM5ZBA for solids loadings of 20, 30, and the shaft to the first separation as described in App- 4095. MMZBA was analyzed and HPLC analysis showed that 1 was obtained by loading 2700g of 99-10095 area without detecting any significant water and 300g of MM5BA into a glass round reaction mixture. The technical output for the batches was 89 vessels with a capacity of 5 liters when mixed at 91905 from the original crude MM5BA. This substance was converted into mesotrione at ambient temperature, which showed a negative result in the Ames test with the subsequent addition of 187g. 2595 Mahon solution through the dropping funnel to

Example 4 of obtaining a pH of 3.220.1 with the formation of a transparent

Method of double selection. mishi Stirring was continued at moderate

This example illustrates the purification of 2-nitro-4-rate at ambient temperature of sulfur-methylsulfonyl benzoic acid by the method of "meadow (20-25"C). This solution was filtered (350 g of double separation of the specified solution) at a pH of 3.2 through a Buch funnel equipped with filter paper

UMpantap 25 (2.5 microns) under vacuum at a temperature of 20-2576. Then the filtrate was returned to the reactor and the ambient temperature. temperature was raised to 90"C. The reactor slowly

The mother liquor was then loaded (pH 3.2) into 4095 Nae5O4 solution was loaded to prove the reaction vessel with a capacity of 1 liter, which is equipped with a pH of the mixture from 3.2 to 1.0240.2, followed by cooling with a slow-moving stirrer with TeyopF blades, a thermometer up to 60"C. The beginning of formation

Tpept-o-Maisn sopigoeg I2E, heating skin- crystals MMOVA should take place at tide and condenser. The mixture was heated for 5 minutes to 857°C. Cooling from 60°C to 20-257°C minutes at 90°C with moderate stirring. continued under cold water or on ice-

10.0 g of activation bath was added to this hot mixture. of coal and stirred for 1 hour. Then the suspension was filtered through a funnel at 90"C (optional). Then Buchner's mixing with U/paitap 44 filter paper was stopped and the mixture was filtered through a funnel, the wet solid element was washed twice with 100 ml

Sintered glass kit with medium porosity of tap water. The solids were then dried at 90"C under vacuum conditions to remove coal. in a vacuum oven at 60"C for 8 hours.

The coal was washed twice with 25 ml of tap water.

Computer layout V. Klyukin Signature Circulation 26 approx.

Ministry of Education and Science of Ukraine

State Department of Intellectual Property, str. Urytskogo, 45, Kyiv, MSP, 03680, Ukraine

SE "Ukrainian Institute of Industrial Property", str. Glazunova, 1, Kyiv - 42, 01601